Dental plaque plays an important role in causing caries and periodontal diseases and for years, extensive efforts have been expended in search of effective antiplaque agents from a wide variety of sources for prevention and treatment of these diseases. Although selected antimicrobial and antiseptic chemicals have been incorporated into dentifrices, the incorporation of plant-derived antimicrobials into such products has only begun recently in the United States. We have demonstrated that methanol extracts from roots of a higher plant commonly used in folk medicine and as a component of a Chinese dentifrice, Zanthoxylum nitidum (ZN), exhibited antimicrobial activity against periodontal pathogens and several species of oral streptococci. Bioassay-guided thin layer chromatography analysis of methanol extracts revealed at least four major active components, one being a plant alkaloid, nitidine. It demonstrated differential inhibitory activity against periodontal pathogens. The overall hypothesis underlying this research is that compounds offering significant antimicrobial and antiplaque properties can be isolated from plant sources. The specific aims of this study are: (i) to fractionate, isolate and identify further antimicrobial components from methanol extract of ZN roots. Methanol extracts of ZN will be fractionated systematically into groups of related polarity. The bioactive subfraction(s) against periodontal pathogens will then be subjected to thin layer chromatographic resolution. The active components will be purified to homogeneity and identified on the basis of their physical and chemical properties. Their structure(s) will be elucidated and confirmed by spectroscopic studies. (ii) to determine the antimicrobial activity of the purified compounds against selected periodontal pathogens. The minimum inhibitor and bactericidal concentrations of the purified compounds against selected periodontal pathogens will be determined and compared with those of standard antimicrobial agents. Time-kill studies will also be performed. (iii) to evaluate the antimicrobial activity of the purified compounds in combinations. As combinations of antimicrobial agents may exert a superior effect and be more effective than a single agent, the effects of the purified antimicrobial components from ZN, in combination, on periodontal bacteria will be examined. This study will provide a scientific explanation for traditional medicine as well as useful methods for future development of natural antiplaque agents from plant species. Such studies may ultimately lead to the discovery of safer, more effective compounds for the prevention and treatment of dental diseases.